全文获取类型
收费全文 | 1142篇 |
免费 | 68篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 23篇 |
儿科学 | 62篇 |
妇产科学 | 41篇 |
基础医学 | 138篇 |
口腔科学 | 13篇 |
临床医学 | 95篇 |
内科学 | 210篇 |
皮肤病学 | 24篇 |
神经病学 | 38篇 |
特种医学 | 142篇 |
外科学 | 24篇 |
综合类 | 19篇 |
预防医学 | 90篇 |
眼科学 | 21篇 |
药学 | 30篇 |
肿瘤学 | 242篇 |
出版年
2022年 | 4篇 |
2021年 | 8篇 |
2019年 | 7篇 |
2018年 | 17篇 |
2017年 | 9篇 |
2016年 | 13篇 |
2015年 | 20篇 |
2014年 | 28篇 |
2013年 | 29篇 |
2012年 | 40篇 |
2011年 | 34篇 |
2010年 | 39篇 |
2009年 | 35篇 |
2008年 | 37篇 |
2007年 | 39篇 |
2006年 | 44篇 |
2005年 | 29篇 |
2004年 | 32篇 |
2003年 | 22篇 |
2002年 | 25篇 |
2001年 | 24篇 |
2000年 | 29篇 |
1999年 | 21篇 |
1998年 | 45篇 |
1997年 | 53篇 |
1996年 | 52篇 |
1995年 | 40篇 |
1994年 | 22篇 |
1993年 | 28篇 |
1992年 | 19篇 |
1991年 | 32篇 |
1990年 | 21篇 |
1989年 | 39篇 |
1988年 | 37篇 |
1987年 | 37篇 |
1986年 | 36篇 |
1985年 | 24篇 |
1984年 | 12篇 |
1983年 | 14篇 |
1982年 | 11篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 7篇 |
1978年 | 12篇 |
1977年 | 9篇 |
1976年 | 7篇 |
1975年 | 11篇 |
1972年 | 3篇 |
1971年 | 5篇 |
1970年 | 4篇 |
排序方式: 共有1212条查询结果,搜索用时 15 毫秒
21.
22.
Jane Topolovec-Vranic Marlene Santos Andrew J Baker Orla M Smith Karen EA Burns 《Canadian respiratory journal》2014,21(5):293-296
INTRODUCTION:
Alterations from first-party and surrogate decision-maker consent can enhance the feasibility of research involving critically ill patients.OBJECTIVE:
To describe the use of a deferred-consent model to enable participation of critically ill patients in a minimal-risk biomarker study.METHODS:
A prospective observational study was conducted in which serum biomarker samples were collected three times daily over the first 14 days following aneurysmal subarachnoid hemorrhage. Sample collection was initiated on intensive care unit admission and consent was obtained when research personnel could approach the patient or the patient’s surrogate decision maker.RESULTS:
Twenty-seven patients were eligible for the study, of whom only five were capable of providing informed consent. Full consent was obtained for 21 (78%) patients through self- (n=4) and surrogate (n=17) consent. Partial consent or refusal (only permitting the collection of blood samples as a part of routine care or use of data) occurred in three patients. Among the 22 consents sought from surrogates, three (11%) refused participation. The refusals included the sickest patients in the cohort. Once consent was provided, no patient or surrogate withdrew consent before study completion.DISCUSSION:
Use of a deferred consent model enabled participation of critically ill patients in a minimal-risk biomarker study with no withdrawals.CONCLUSIONS:
Further research and enhanced awareness of the potential utility of hybrid models, including deferred consent in addition to patient or surrogate consent, in the conduct of low-risk and minimally interventional time-sensitive studies of critically ill patients are required. 相似文献23.
Gaudet MM Falk RT Stevens RD Gunter MJ Bain JR Pfeiffer RM Potischman N Lissowska J Peplonska B Brinton LA Garcia-Closas M Newgard CB Sherman ME 《The Journal of clinical endocrinology and metabolism》2012,97(9):3216-3223
Context: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk assessment, and understanding etiology. Objective: The objective of the study was to evaluate the reliable measurement of metabolites in epidemiological studies with nonstandardized blood collection; confirm previously reported correlations of metabolites with body size; and assess differences in metabolite levels between cases and controls. Design: This was the Polish Endometrial Cancer Study (2001-2003). Setting: This study was a population-based case-control study. Patients: Patients included 250 cases and 250 controls. Intervention: The intervention included the measurement of serum metabolite levels of 15 amino acids, 45 acylcarnitines, and nine fatty acids. Main Outcome Measure: The main outcome measure was endometrial cancer. Results: Body mass index was correlated with levels of valine (r = 0.26, P = 3.4 × 10(-5)), octenoylcarnitine (r = 0.24, P = 1.5 × 10(-4)), palmitic acid (r = 0.26, P = 4.4 × 10(-5)), oleic acid (r = 0.28, P = 9.9 × 10(-6)), and stearic acid (r = 0.26, P = 2.9 × 10(-5)) among controls. Only stearic acid was inversely associated with endometrial cancer case status (quartile 4 vs. quartile 1: odds ratio 0.37, 95% confidence interval 0.20-0.69, P for trend = 1.2 × 10(-4)). Levels of the C5-acylcarnitines, octenoylcarnitine, decatrienoylcarnitine, and linoleic acid were significantly lower in cases than controls (odds ratios ranged from 0.21 to 0.38). Conclusions: These data demonstrate that previously reported variations in metabolomic profiles with body mass index can be replicated in population-based studies with nonfasting blood collection protocols. We also provide preliminary evidence that large differences in metabolite levels exist between cases and controls, independent of body habitus. Our findings warrant assessment of metabolic profiles, including the candidate markers identified herein, in prospectively collected blood samples to define biomarkers and etiological factors related to endometrial cancer. 相似文献
24.
25.
Reiman EM Brinton RD Katz R Petersen RC Negash S Mungas D Aisen PS 《The journals of gerontology. Series A, Biological sciences and medical sciences》2012,67(7):766-772
What will it take to develop interventions for the treatment of age-related cognitive decline? Session V of the Summit provided perspectives on the design of clinical trials to evaluate promising but unproven interventions, and some of the steps needed to accelerate the discovery and evaluation of promising treatments. It considered strategies to further characterize the biological and cognitive changes associated with normal aging and their translation into the development of new treatments. It provided regulatory, scientific, and clinical perspectives about neurocognitive aging treatments, their potential benefits and risks, and the strategies and endpoints needed to evaluate them in the most rapid, rigorous, and clinically meaningful way. It considered lessons learned from the study of Alzheimer's disease, the promising roles of biomarkers in neurocognitive aging research, and ways to help galvanize the scientific study and treatment of neurocognitive aging. 相似文献
26.
27.
Pratima Kumari Hussin A. Rothan Janhavi P. Natekar Shannon Stone Heather Pathak Philip G. Strate Komal Arora Margo A. Brinton Mukesh Kumar 《Viruses》2021,13(1)
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can cause neurological disease in humans, but little is known about the pathogenesis of SARS-CoV-2 infection in the central nervous system (CNS). Herein, using K18-hACE2 mice, we demonstrate that SARS-CoV-2 neuroinvasion and encephalitis is associated with mortality in these mice. Intranasal infection of K18-hACE2 mice with 105 plaque-forming units of SARS-CoV-2 resulted in 100% mortality by day 6 after infection. The highest virus titers in the lungs were observed on day 3 and declined on days 5 and 6 after infection. By contrast, very high levels of infectious virus were uniformly detected in the brains of all the animals on days 5 and 6. Onset of severe disease in infected mice correlated with peak viral levels in the brain. SARS-CoV-2-infected mice exhibited encephalitis hallmarks characterized by production of cytokines and chemokines, leukocyte infiltration, hemorrhage and neuronal cell death. SARS-CoV-2 was also found to productively infect cells within the nasal turbinate, eye and olfactory bulb, suggesting SARS-CoV-2 entry into the brain by this route after intranasal infection. Our data indicate that direct infection of CNS cells together with the induced inflammatory response in the brain resulted in the severe disease observed in SARS-CoV-2-infected K18-hACE2 mice. 相似文献
28.
Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans 总被引:3,自引:0,他引:3
Granowitz EV; Porat R; Mier JW; Orencole SF; Callahan MV; Cannon JG; Lynch EA; Ye K; Poutsiaka DD; Vannier E 《Blood》1993,82(10):2985-2990
Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra. 相似文献
29.
The balance of tissue-type plasminogen activator (t-PA) production and degradation determines its concentration in blood and tissues. Disturbance of this balance may result in either increased or decreased proteolysis. In the present study, we identified the receptor systems involved in the degradation of t-PA by human monocytes/macrophages in culture. Monocytes were cultured and became macrophages within 2 days. At 4 degrees C, 125I-t-PA bound to macrophages with high (apparent dissociation constant [kd], 1 to 5 nmol/L) and low affinity (kd > 350 nmol/L). At 37 degrees C, the cells internalized and degraded t-PA via the high affinity binding sites, which were partially inhibited by mannan. The low affinity binding sites were 6-aminohexanoic acid- inhibitable and not involved in t-PA degradation. Degradation of t-PA was upregulated during differentiation of monocytes to macrophages. Dexamethasone further upregulated the mannan-inhibitable t-PA degradation. Lipopolysaccharide downregulated both mannan-inhibitable and non-mannan-inhibitable t-PA degradation. Non-mannan-inhibitable degradation was completely blocked by recombinant 39-kD receptor- associated protein (RAP, inhibitor of lipoprotein receptor-related protein [LRP]), whereas mannan-inhibitable degradation was blocked by the addition of a monoclonal antibody against the mannose receptor. No differences between the degradation of t-PA and functionally inactivated t-PA were observed. We conclude that human monocyte-derived macrophages are able to bind, internalize, and degrade t-PA. Degradation of t-PA does not require complex formation with plasminogen activator inhibitors. The macrophages use two independently regulated receptors, namely, the mannose receptor and LRP, for the uptake and degradation of t-PA. 相似文献
30.
Tara M. Connelly Arthur S. Berg Leonard R. Harris III John P. Hegarty Francesca M. Ruggiero Susan M. Deiling David L. Brinton Walter A. Koltun 《The Journal of surgical research》2014